Absence of effect of chronic nicotine administration on amyloid beta peptide levels in transgenic mice overexpressing mutated human APP (Sw, Ind).
Studies have indicated that nicotine has disease-modifying and cognitive-enhancing properties in Alzheimer's disease (AD). Nicotine has been proposed to be neuroprotective through anti-amyloid beta (Abeta) effects, anti-excitotoxic effects, and anti-free radical effects. Previously, conflicting data from Abeta plaque developing transgenic mice have shown significant Abeta-lowering effects, or alternatively no effects, of nicotine administration. In this study, dosing of transgenic mice (J20 strain) with mutated human APP (Swedish mutations: K670N and M671L and Indiana mutation: V717F) transgene, with nicotine in drinking water for 20 weeks did not have a significant effect on total levels of Abeta 40 or 42 in hippocampus or cortex. This treatment strategy resulted in increased levels of nicotinic acetylcholine receptor activity, and reduced levels of cortical glial fibrillary acidic protein, but had no effect on cortical synaptophysin protein levels. The J20 mouse strain produces higher levels of Abeta 42, the more pathogenic form of Abeta, than Abeta 40 compared to other Abeta plaque developing mouse strains; this could account for differences in effectiveness of nicotine in transgenic mice models of AD.
Sabbagh
Marwan N
MN
Cleo Roberts Center for Clinical Research, Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85351, USA. marwan.sabbagh@bannerhealth.com
Walker
Douglas G
DG
Reid
Richard T
RT
Stadnick
Tiffany
T
Anand
Keshav
K
Lue
Lih-Fen
LF
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D009154:Mutation; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism*; D058255:Protease Nexins; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism
C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D018722:Nicotinic Agonists; D010446:Peptide Fragments; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D011978:Receptors, Nicotinic; C503968:Synpo protein, mouse; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D009538:Nicotine